(UroToday.com) In the on-demand poster session of the European Society for Medical Oncology (ESMO) Annual Congress, Emeline Colomba presented results from the ODENZA trial comparing darolutamide and enzalutamide, with a focus on cognitive assessment. Each of these agents is a next-generation androgen receptor inhibitor. However, darolutamide does not significantly penetrate the blood-brain barrier, which may reduce cognitive impairment.
ODENZA is a prospective, cross-over, preference, randomized phase II trial of darolutamide and enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC). Previous reports of this trial showed that numerically more pts with early mCRPC preferred darolutamide over enzalutamide, although the difference did not reach significance.
To summarize the methodology, 249 patients were randomized 1:1 to receive darolutamide 1200 mg/d for 12 weeks followed by enzalutamide 160 mg/d for 12 weeks or the reverse sequence. In this analysis of the key secondary endpoint, cognitive assessment using computerized cognitive tests (COGSTATE) was performed. Changes from baseline were described by assessing each 12 weeks period. Individual tests (Detection Test: psychomotor function, Identification Test: visual attention, One Back Test: working memory, International Shopping List Test (ISL): verbal learning, International Shopping list Test Delayed Recall (ISRL): verbal memory, Groton Maze Learning: executive function) were used and three composite scores (eg ISL/ISRL for episodic memory) were created.
The authors examined treatment effects using Mixed-Effects Model Repeated Measures. Effect sizes were classified as clinically meaningful when greater than or equal to 0.5.
Among 249 patients enrolled in the trial, cognitive data were available in 193 patients. Performance on verbal learning (ISL) was significantly better with darolutamide at each of the post-baseline assessments, within both periods and when averaged over periods. Further, these effects were clinically meaningful at the second period (-0.62, p=0.0001) and overall (-0.54, p<0.0001).
Performance on verbal memory (ISRL) was significantly better with darolutamide at the second period and when averaged over periods, although the effect sizes were less meaningful (second period: -0.4, p=0.01 and overall: -0.29, p=0.0075). No difference in other tests was found. Additionally, the composite scores reported a moderate benefit in episodic memory after treatment with darolutamide compared to enzalutamide.
The authors, therefore, conclude that, in early mCRPC, darolutamide was associated with a statistically significant benefit in verbal learning and verbal memory compared to enzalutamide.
Presented by: Emeline Colomba, MD, Gustave Roussy, Villejuif, France